Adriamycin heart muscle disease as it develops in the rabbit is a good model of human adriamycin heart muscle disease and of congestive heart failure. The functional, morphological and metabolic integrity of the rabbit myocardium will be quantified over the 8 to 10 weeks required to produce florid cardiac degeneration and failure using a dose of 2.25 mg/kg per week given intravenously to New Zealand white rabbits. Myocardial functional and metabolic integrity will be correlated with biochemical studies aimed at determining specific alterations in subcellular systems. Measurements will be made of serum and myocardial adriamycin levels and of myocardial calcium and other electrolytes. The isolated perfused interventricular septal preparation will be used for studies of contractile function, plasma membrane integrity (ionic lanthanum probe technique) and intracellular electrolyte alterations (analytical electron microscopy). High energy phosphate levels in functioning myocardium will be determined by nuclear magnetic resonance. Biochemical studies will include measurements of myofibrillar ATPase, myosin structure and function, mitochondrial oxidative phosphorylation, Ca2+ flux in isolated vesicles of sarcolemma and sarcoplasmic reticulum, membrane phospholipids and lipid peroxidation. Additional groups of rabbits will be studied to establish an association or disassocation between the various measured parameters and the reversal, amelioration or delayed progression of adriamycin heart muscle disease. The basic hypothesis underlying these studies is that a subcellular or membrane functional alteration precedes and then plays a causal role in the development of structural heart muscle damage and congestive heart failure secondary to recurrent adriamycin treatment.